TABLE 1.
Available copper complexes as UPS inhibitors.
| Target | Agents | Tumor Models | Effects | Refs |
|---|---|---|---|---|
| 20S proteasome | CuHQ | HL-60, Jurkat T, MCF10DCIS.com, and NK (YT) cells | Induces PARP1 cleavage, induces Ub accumulation, and increases BAX | Daniel et al. (2004), Zhai et al. (2010) |
| 20S proteasome | CuCQ | MCF10DCIS.com and MDA-MB-231 cells | Induces PARP1 cleavage, induces Ub accumulation, and increases BAX | Daniel et al. (2005), Zhai et al. (2010) |
| 20S proteasome | CuPDTC | MCF10DCIS.com, MDA-MB-231, and LNCaP cells | Induces PARP1 cleavage, induces Ub accumulation, and increases NFKBIA, CDKN1B, and BAX | Chen et al. (2005), Daniel et al. (2005), Yu et al. (2007), Milacic et al. (2008) |
| 20S proteasome NPLOC4 | CuET | MCF10DCIS.com, MDA-MB-231 cells, and U2OS cells; MDA-M-231 xenograft | Induces Ub accumulation, increases NFKBIA, CDKN1B, and BAX, and induces apoptotic and non-apoptotic cell death | Chen et al. (2006), Cvek et al. (2008), Skrott et al. (2017) |
| 20S proteasome | Cu(I)ET | BXPC-3, PANC-1, and SW 1990 cells; SW 1990 cells xenograft | Induces Ub accumulation, increases CDKN1B, and deceases NFKB | Han et al. (2013) |
| 20S proteasome | FPA-137 | LNCaP and PC-3 cells | Induces PARP1 cleavage, and induces Ub accumulation | Adsule et al. (2006) |
| 20S proteasome | Compound 1 | Jurkat T and MDA-MB-231 cells | Induces PARP1 cleavage, induces Ub accumulation, and increases CDKN1B and BAX | Zhang (2008) |
| 20S proteasome | GVC | Jurkat T, MCF10DCIS.com, and MDA-MB-231 cells | Induces PARP1 cleavage, induces Ub accumulation, and increases NFKBIA | Xiao et al. (2008) |
| 20S proteasome | Cu(LI)Cl | C4-2B and Jurkat T cells | Induces PARP1 cleavage and induces Ub accumulation | Hindo et al. (2009) |
| 20S proteasome | CuNC | Jurkat T and MDA-MB-231 cells | Induces PARP1 cleavage, induces Ub accumulation, and increases NFKBIA | Xiao et al. (2010) |
| 20S proteasome | Complexes C1 | MCF-7, MDA-MB-231, and PC-3 cells | Induces PARP1 cleavage, induces Ub accumulation, increases NFKBIA and BAX, and decreases XIAP | Zuo et al. (2013) |
| 20S proteasome | Cu(OH-PIP) (Phe)Cl | CAL-51, MCF-7, and MDA-MB-231 cells | Induces PARP1 cleavage, induces Ub accumulation, increases BAX, and decreases pro-CASP3 and BCL2 | Li et al. (2019b) |
| 20S proteasome | Cu2(sal-D,L-glu)2 (isoquinoline)2 | A549, HeLa, and U-118MG cells | Induces cytotoxicity | Konarikova et al. (2019) |
| UCHL5 and USP14 | CuPT | HepG2, MCF-7, NCI-H929, SMMC-7721, and U266 cells; HepG2 xenograft | Induces PARP1 cleavage, induces Ub accumulation, increases CDKN1A, CDKN1B, BAX, and NFKBIA, and decreases pro-CASP8 and pro-CASP9 | Liu et al. (2014a) |
| UCHL5 and USP14 | CuHK | A549 and K562 cells | Induces PARP1 and CASP3 cleavage, induces Ub accumulation, increases ATF4, and induces paraptosis | Chen et al. (2017) |
Abbreviations: ATF4, activating transcription factor 4; BAX, bcl2 associated X, apoptosis regulator; BCL2, bcl2 apoptosis regulator; CASP3, caspase 3; CASP8, caspase 8; CASP9, caspase 9; CDKN1A/p21, cyclin dependent kinase inhibitor 1A; CDKN1B/p27, cyclin dependent kinase inhibitor 1B; NFKBIA/IKBA, NFKB inhibitor alpha; NPLOC4, NPL4 homolog, ubiquitin recognition factor; PARP1/PARP, poly(ADP-ribose) polymerase 1; Ub, ubiquitin; UCHL5/UCH37, ubiquitin C-terminal hydrolase L5; USP14, ubiquitin-specific peptidase 14; XIAP, X-linked inhibitor of apoptosis.